The Mystery Deepens

By MICHAEL D. LEMONICK

The theory about how the country's anthrax attack unfolded last month seemed pretty plausible. Yes, the story had loose ends, but the basic idea was that anyone who'd come down with the disease had either been in direct contact with letters laced with spores or had been in a room that a letter passed through.

That was before Kathy Nguyen died. On Thursday, Oct. 25, the Vietnamese-born hospital worker came down with chills and muscle aches. She went to work Thursday and Friday at the stockroom of the Manhattan Eye, Ear & Throat Hospital on Manhattan's Upper East Side. But the symptoms worsened, and on Sunday she was hospitalized with severe breathing problems, fluid in her lungs, sputum tinged with blood and a 102[degree]F fever. By last Wednesday, Nguyen had succumbed to a galloping case of inhalational anthrax. She was 61.

What makes Nguyen's case so baffling is that she didn't fit any of the profiles of a potential anthrax victim. She didn't work in a post office or for the media, which have been the targets of at least three anthrax-laden letters. The stockroom where she worked adjoins the mailroom, and she did occasionally handle mail. But no suspicious letters turned up at the hospital. And tests have found no signs of anthrax either at her workplace or her apartment in the Bronx, where she lived alone. Nasal swabs of people who worked with or near Nguyen have come back negative as well.

In fact, after 17 cases and four deaths, officials are coming to the realization that they know little about anthrax in general and about this attack in particular. Anthrax spores have been detected at a widening list of sites. In the past week they showed up for the first time at a mailroom in the Washington, D.C., V.A. Medical Center; a postal facility in Kansas City, Mo.; a shop in Indianapolis, Ind., that repairs postal machines; a third New Jersey post office and a sixth in Florida; in four mailrooms at the Food and Drug Administration in Rockville, Md.; at a newspaper in Pakistan; and at the U.S. embassies in Peru and Lithuania.

But at the same time, the number of new anthrax infections has grown by only three--Nguyen's, and cases of skin anthrax that struck a New Jersey woman and a New York Post employee. Because the first two people evidently had no direct exposure to any of the known anthrax letters, nor were they known to have spent significant periods of time in the post offices that handled them, it has become increasingly hard to figure out what's going on. Maybe it's a lot easier to get the disease than the experts thought, or maybe some individuals are particularly susceptible. Maybe more letters went out than the authorities yet know about. Or maybe both women are the first victims of an entirely new form of attack that has nothing to do with the mail.

According to the conventional wisdom about anthrax, it takes 8,000 to 10,000 spores to trigger a case of inhalational anthrax. And while the letter that arrived at Senator Tom Daschle's office probably contained billions of spores, they would have to be aerosolized first--puffed into an inhalable cloud. That's easy enough to do in an envelope if there is even a small opening and enough pressure, such as that generated by a mail-sorting machine. Any gaps in the tape that sealed the Daschle letter, or even the porosity of the envelope, therefore, could explain the inhalational-anthrax cases at the post offices the Daschle letter passed through.

But that doesn't explain how a postal worker in the State Department mail-processing center got the disease or how Nguyen contracted it. Anthrax puffed from an envelope could easily settle on mail-processing machines--where spores have been found--or on other surfaces. They could also have settled on other letters, in what's known as cross-contamination. Anyone touching a cross-contaminated letter, especially someone with an open cut, would be at risk for skin anthrax--and in fact, the New Jersey woman's mailbox tested positive late last week, suggesting that this might be what happened to her.

But in order to be inhaled, cross-contaminated spores would have to be re-aerosolized, and that is hard to imagine, says William Patrick, a longtime Army biological-weapons researcher. "There's an electrostatic bond between the spore and the envelope," he says. "It takes a lot of energy to break the bond. They're just not going to be re-aerosolized in large enough quantities to provide an inhalation case." That would suggest that more than the three known letters have passed through the system. And given the tens of thousands of pieces of mail still impounded in Washington and New Jersey, some of them could still be there.

But it's also possible that the conventional wisdom is wrong. The only hard data on how many spores it takes to cause inhalational anthrax come from studies the Army did on monkeys in the 1950s. When the dose was 8,000 to 10,000 spores per animal, about half the monkeys died. But that doesn't prove that a lot fewer spores won't cause an infection. Says Philip Brachman, a professor of public health at Emory University who investigated a naturally occurring 1957 outbreak in Manchester, N.H., among millworkers who handled infected animal hides: "We don't know for certain what dosage of the organisms causes inhalation anthrax."

In fact, says Harvard's Matthew Meselson, a Nobel-prizewinning biologist who did an in-depth study of an anthrax accident at a Soviet bioweapons plant in Sverdlovsk in 1979, "there is no theoretical or experimental basis to believe in any sort of minimum threshold." A dozen or even fewer spores could be sufficient to kill, he suspects, under the right circumstances.

What those might be is also anybody's guess. "There have been cases," says Meselson, "where a man works in a factory with anthrax spores and doesn't get sick, but comes home, takes off his clothes, and his wife gets inhalation anthrax. There are also cases where a person waiting for a bus some distance away from a factory where spores are known to exist gets inhalation anthrax, although not all workers in the factory do." It may have to do with how deeply an individual breathes in the spores or with his or her overall respiratory health. It might even be related to age. So far, the vast majority of fatal inhalational-anthrax cases, both in the past few weeks and in the Soviet accident, occurred in victims who were at least 40 years old.

Another confounding factor has to do with the behavior of anthrax particles. Ken Alibek, who ran the Soviet and Russian biological-weapons program until 1992 and later defected to the U.S., says that aerosolized anthrax can travel in unpredictable ways. The weapons-grade powder he worked with, he recalls, kept turning up in odd places in the labs. This also seems to be happening at the Brentwood mail facility outside Washington, which processed the Daschle letter. The CDC's contamination map of the building reveals several different locations where anthrax was found, in no discernible pattern.

Yet another question is the incubation period of the spores. Evidence from the Sverdlovsk accident indicates that victims can develop symptoms as long as 45 days after exposure--suggesting that more victims could still show up in the U.S.

If anthrax really can move around erratically and cause disease at very low concentrations, Kathy Nguyen's death becomes far easier to explain. Her mail might have passed through the Morgan postal station in New York City, for example, where letters to NBC and the New York Post were handled, or she might have had some sort of contact with someone who worked there. On the other hand, some FBI agents are convinced that their best lead in the case is lurking somewhere in the last weeks of Nguyen's life. "This is the hot one," says an agent. "If we can figure out what's staring us in the face, it'll break it. It's got to be an apartment near her, or somebody where she worked or someplace she went."

Unfortunately, it won't be easy to reconstruct Nguyen's movements over the past few weeks: by the time her disease was diagnosed she was on a respirator and heavily sedated. She died before she could be questioned.

Meanwhile, scientists are making the best use of the data pouring in. "This is new ground," says Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. "Years from now, people will look at our experience and say, 'Ah, we know spores can do A, B, C, D and E, but in October 2001, they weren't sure of that.'" Like many experts, Fauci is willing to consider that anthrax may be far easier to catch than anyone thought--but like his counterparts on the criminal side of the investigation, he's also open to the idea that terrorists have been releasing spores in other ways.

Meanwhile, Meselson and others believe there might be a pattern in the attacks so far. Focusing on the three letters postmarked Trenton, N.J., they note that the first two, mailed Sept. 18, contained a relatively crude form of anthrax and caused mostly skin infections. The third, mailed to Daschle on Oct. 9, carried more potent spores; infections plausibly caused by that letter were mostly inhaled. Meselson has proposed that the initial mailings could represent the first two tentative steps in a diabolical experiment that's not over yet.

If so, a third and potentially far more lethal step could still be in the works. Even experienced bioweapons experts were surprised to learn how much weapons-grade anthrax showed up in Daschle's office; they don't even want to guess how many people might have been infected if it had got into the building's ventilation system. For now, authorities are keeping their eyes on crop dusters and skyscraper air vents, but if someone managed to puff a good-size cloud of anthrax into a large, enclosed area--a basketball arena, say, or a city subway system--the death toll could be in the hundreds or even thousands.

--Reported by Andrea Dorfman, Stephen Handelman and Alice Park/New York City and Elaine Shannon and Andrew Goldstein/Washington

With reporting by Andrea Dorfman, Stephen Handelman and Alice Park/New York City and Elaine Shannon and Andrew Goldstein/Washington